Work has been going on for many years on methods for increasing the radiosensitivity of tumors relative to that of normal tissues. One of these methods involves administering a pharmaceutical that sensitizes the tumor cells to radiation. The use of such pharmaceuticals, called radiosensitizers, provides a potentially cheap technique of increasing the radiosensitivity of tumors that can be used with existing radiation therapy equipment without any need to invest in additional equipment.
The largest class of radiosensitizers is the hypoxic cell sensitizers. These pharmaceuticals overcome the radioresistance afforded some tumor cells by their lack of oxygen (hypoxia). Within this class electron-affinic nitroimidazoles have been found in general to radiosensitize hypoxic tumor cells. Two nitroimidazoles, misonidazole and metronidazole, have been deemed suitable for clinical use. "Optimization of Radiotherapy", WHO Technical Report Series 644, World Health Organization, 1980. Misonidazole (hereinafter designated MIS) appears to have the greater radiosensitizing activity of the two compounds. Even so, its clinical applications are limited by its neurotoxicity and a total dose not exceeding 12 g/m.sup.2 of body surface is recommended in man. Dische, et al, "Clinical Testing of Radiosensitizer RO 07-0582: Experience with Multiple Doses", Br J Cancer 35, 567-79, 1977. When used at this dose rate with each fraction of a conventional multifraction radiotherapy regime, MIS achieves suboptimal radiosensitization. Thus, there is clearly a need for effective radiosensitizers that are less toxic than MIS.